Worldwide oral cancer is the 6th commonest cancer and 5-year survival rates following diagnosis remain around 50% globally (63% in the USA) but have only shown limited improvements since the 1970s. There has been a marked increase in research into molecularly targeted therapies and these may have benefits for treating oral cancers although their value is unclear.

The aim of this Cochrane review was to assess the effects of molecularly targeted therapies and immunotherapies, in addition to standard therapies, for the treatment of oral cavity or oropharyngeal cancers.

Two reviewers independently screened the studies, extracted data and assessed risk of bias using the Cochrane risk of bias tool. The primary outcome was total mortality expressed as a hazard ratio (HR)

There was also moderate quality evidence that EGFR mAb may result in 32% fewer locoregional failures when added to radiotherapy (RT) (HR 0.68; 95% CI 0.52 to 0.89; 424 participants, one study, 60% oropharyngeal tumours).

A subgroup analysis separating studies by type of standard therapy (radiotherapy (RT) or chemoradiotherapy (CRT)) showed some evidence that adding EGFR mAb therapy to RT may result in a 30% reduction in the number of people whose disease progresses (HR 0.70; 95% CI 0.54 to 0.91; 424 participants, one study, 60% oropharyngeal tumours, unclear risk of bias). For the subgroup comparing EGFR mAb plus CRT with CRT alone there was insufficient evidence to determine whether adding EGFR mAb therapy to CRT impacts on progression-free survival (HR 1.08; 95% CI 0.89 to 1.32; 891 participants, one study, 70% oropharyngeal tumours, high risk of bias). The high subgroup heterogeneity meant that we were unable to pool these subgroups.

There was evidence that adding cetuximab to standard therapy may result in increased skin toxicity and rash (RR 6.56; 95% CI 5.35 to 8.03; 1311 participants, two studies), but insufficient evidence to determine any difference in skin toxicity and rash in the case of nimotuzumab (RR 1.06; 95% CI 0.85 to 1.31; 92 participants, one study).

Conclusions

The authors concluded:

We found some evidence that adding EGFR mAb to standard therapy may increase overall survival, progression-free survival and locoregional control, while resulting in an increase in skin toxicity for some mAb (cetuximab).

There is insufficient evidence to determine whether adding TKIs to standard therapies changes any of our primary outcomes.

Very low quality evidence from a single study suggests that rIL-2 combined with surgery may increase overall survival compared with surgery alone.

Comments

This is the 4th in a series of Cochrane reviews looking at different treatments for oral cancer, surgery (Bessell et al, 2011), radiotherapy (Glenny et al, 2010) and chemotherapy (Furness et al ,2011). It has been conducted following the usual Cochrane protocols. Ten out of the 12 included trials were multicenter studies with 4 studies involving more than one country. While all of the studies reported overall survival HR for mortality could only be calculated for 6 studies and only 2 reported on disease free survival and only one study comprehensively assessed quality of life.

Surgery and radiotherapy or a combination and the usual treatment for early stage oral cancer with chemoradiotherapy and sequential therapies rather than surgery for advanced cases. This review suggests that monoclonal antibodies (mAb) against the epidermal growth factor receptor (EGFR) in combination with standard treatment may improve outcomes. However, as the authors note the evidence for these therapies is still sparse and none of the included studies many of which were conducted by pharmaceutical companies, was at low risk of bias so further high quality studies are needed.

Derek Richards is the Director of the Centre for Evidence-based Dentistry, Editor of the Evidence-based Dentistry Journal, Consultant in Dental Public Health with Forth Valley Health Board and Honorary Senior Lecturer at Dundee & Glasgow Dental Schools. He helped to establish both the Centre for Evidence-based Dentistry and the Evidence-based Dentistry Journal. He has been involved with teaching EBD and a wide range of evidence-based initiatives both nationally and internationally since 1994.